Adverse and beneficial effects of tocolytic therapy.

In addition to questions raised about the efficacy of many tocolytics, appropriate concern has been voiced about the safety of these potent drugs. Although some degree of risk for adverse effects with drugs promising a strong therapeutic effect can be accepted, caution needs to be exercised when benefits are marginal or unproven. Unfortunately, some of the tocolytics, most notably the betamimetics and magnesium sulfate, have been found to have considerable potential for adverse maternal cardiovascular and respiratory effects. Although less clearly established, the use of indomethacin appears to be associated with increased fetal and neonatal risks. Concerning magnesium sulfate, in addition to the well-known maternal effects, the accumulating evidence showing an increased frequency of adverse outcomes in the fetus and neonate has led to the recommendations to abandon its use entirely as a tocolytic. Given the limitations of our current state of knowledge, nifedipine would appear to be among the more efficacious and safer tocolytics available to use when properly indicated.

Neonatal-perinatal risk factors for the development of persistent pulmonary hypertension of the newborn in preterm newborns.

There is a long-held belief that preterm newborns lack sufficient arteriolar musculature to maintain a prolonged elevated pulmonary vascular resistance (PVR) after birth. Net ductal flow is thought to be minimal, with the developing pulmonary circulation incapable of significant vasoconstriction. We identified retrospectively 15 premature newborns over a 10-year period weighing < or = 1500 g and with a gestational age of < or = 30 weeks with documented persistent pulmonary hypertension of the newborn (PPHN) in the first 24 hours after birth. We matched 36 newborns of similar weight and gestation with no clinical evidence of shunting. The control group weaned to an FiO2 < or = 0.50 by 12 hours after birth. Despite similar gestational ages, the PPHN group (n = 15) had significantly higher birth weights than the control group (n = 36). The duration of ruptured membranes, maternal tobacco use, and use of antenatal steroids were significantly higher in the PPHN group. We speculate that these three factors might act in a synergistic relationship with which to accelerate pulmonary vascular smooth muscle development in premature newborns.

Effect of chronic tocolytic therapy on maternal ventricular function in pregnant rabbits.

OBJECTIVE: Our purpose was to determine whether peripartum cardiomyopathy may be associated with chronic beta-mimetic tocolytic therapy. STUDY DESIGN: On gestational day 20 (term 31 days), two 200 microliter Alzet miniosmotic pumps were implanted in the subcutaneous tissue of pregnant New Zealand White rabbits. Each pump was filled with terbutaline (20 micrograms/microliter, n = 7) or saline solution (0.9%, n = 7) and infused continuously for 7 days. The rabbits were killed on the twenty-eighth gestational day. Maternal hearts were placed on a Langendorff (nonejecting) perfusion apparatus for assessment of cardiac function. At a constant perfusion pressure and heart rate left ventricular diastolic pressure was varied while left ventricular developed pressure and left ventricular +/- rate of pressure rise, index values of left ventricular contractility and relaxation, were continuously recorded. Comparisons between groups at each preload were made by analysis of variance. RESULTS: Hearts taken from terbutaline-treated rabbits exhibited periodic arrhythmias and mechanical alternans in five of seven hearts versus one of seven in the saline solution group. At a preload of 0 mm Hg both left ventricular developed pressure (88.0 vs 48.4 mm Hg, p < 0.001) and left ventricular rate of pressure rise (1406 vs 653 mm Hg/sec, p < 0.001) were less in terbutaline-treated rabbits. At a preload of 10 mm Hg left ventricular developed pressure (104.4 vs 56.7 mm Hg, p < 0.01) and rate of pressure rise (1424 vs 694 mm Hg/sec, p < 0.001) were also significantly less in terbutaline-treated rabbits. Left ventricular relaxation was also impaired at all preloads. CONCLUSIONS: In this model chronic administration of terbutaline during late pregnancy significantly depresses global maternal cardiac function.

Effect of dual tocolysis on the incidence of severe intraventricular hemorrhage among extremely low-birth-weight infants.

OBJECTIVE: Our purpose was to evaluate the null hypothesis that dual tocolysis with magnesium sulfate and indomethacin does not alter the rate of grade III or IV intraventricular hemorrhage. STUDY DESIGN: Fifty-six neonates weighing 500 to 800 gm from mothers who received tocolytic therapy with magnesium sulfate alone or in combination with indomethacin were the subjects of this retrospective study. Demographic variables were evaluated with a Student t test, chi(2) analysis, Fisher exact test, or Mantel-Haenszel chi(2) as appropriate. RESULTS: There was an increased incidence of grade III to IV intraventricular hemorrhage among patients treated with dual therapy (p = 0.02). Logistic regression showed that fetal age and dual tocolysis with indomethacin were the only independent prognostic factors for severe intraventricular hemorrhage. CONCLUSION: The results indicate that dual tocolysis with indomethacin may place extremely low-birth-weight infants at increased risk for grade III to IV intraventricular hemorrhage.

The effect of tocolytic use in the management of symptomatic placenta previa.

OBJECTIVE: The null hypothesis is that tocolysis has no effect on pregnancy prolongation in the aggressive expectant management of symptomatic preterm placenta previa. STUDY DESIGN: One hundred twelve preterm pregnancies with confirmed placenta previa and an initial episode of acute vaginal bleeding were selected for this retrospective analysis. Exclusion criteria included gestational age > or = 35 weeks, delivery within 24 hours of admission, prior treatment for bleeding or preterm labor, and contraindications to tocolytic use. Tocolysis was prescribed, at the discretion of the treating clinical staff, in selected pregnancies with significant uterine contractions after admission of the patient. The majority of treated patients (85%) received intravenous magnesium sulfate and/or oral or subcutaneous beta-sympathomimetics within 24 hours of admission. Most patients remained hospitalized until delivery under this aggressive expectant management protocol. Both treated and untreated control study groups were similar at inclusion with regard to parity, gestational age, contraction frequency, and degree of initial bleeding. Outcome variables for each treatment group were obtained from final chart review. Continuous and categoric variables were compared with Student t test or chi 2 analysis-Fisher's exact test, respectively. RESULTS: The clinical use of tocolysis in symptomatic placenta previa was associated with a clinically significant delay of preterm delivery. Significant improvement in clinical parameters such as interval from admission to delivery (39.2 vs 26.9 days, p < 0.02) and birth weight (2520 vs 2124 gm, p < 0.03) was observed in the tocolysis group. There was no observed statistical difference between the two treatment groups with regard to incidence of recurrent bleeding, interval from admission to first recurrent bleeding, and need for transfusion. There was a trend for patients with multiple bleeding episodes to have been receiving tocolytic therapy (p < 0.10). A trend for requiring a postpartum transfusion was also noted in the tocolysis group (p < 0.09). Treated pregnancies receiving long-term maintenance tocolysis with oral or subcutaneous terbutaline exhibited a greater degree of pregnancy prolongation than those treated with short-term intravenous magnesium alone (43.7 vs 15.3 days, p < 0.02). CONCLUSIONS: This retrospective analysis suggests that tocolytic intervention in cases of symptomatic preterm previa may be associated with clinically significant prolongation of pregnancy and increased birth weight. Tocolytic therapy in these cases does not appear to have an impact on frequency or severity of recurrent vaginal bleeding. Further prospective analysis may delineate the role of tocolysis in the aggressive expectant management of symptomatic placenta previa.

Effect of amnioinfusion on the incidence of postpartum endometritis in patients undergoing cesarean delivery.

We reviewed records from 251 consecutive cesarean deliveries performed over a six-month period to evaluate the effect of amnioinfusion during labor on the incidence of postpartum endometritis in patients who delivered by cesarean section. One hundred fifty-four patients were excluded because they were not in labor, were at less than 35 weeks' gestation or received antibiotics during labor. Twenty-three of the remaining 97 patients received amnioinfusion during labor and represented the study group. Seventy-four patients did not receive amnioinfusion during labor and were used as controls. The incidence of postpartum endometritis in the amnioinfusion group was 13%, while the incidence in the group not receiving amnioinfusion was 38% (relative risk, 0.34; 95% confidence interval, 0.13-0.88; P = .026). Amnioinfusion during labor appears to significantly decrease the incidence of postpartum endometritis in patients subsequently undergoing cesarean delivery.

Preterm labor, premature rupture of membranes, and cervical incompetence.

Prematurity continues to account for 75% of perinatal morbidity and mortality in the United States. The search for accurate clinical methods to predict prematurity and the critical evaluation of treatment strategies for premature labor dominate the recent medical literature. Specific clinical issues addressed during the literature review period include critical evaluation of home tocodynamometry, reevaluation and new investigation into tocolytic agents, clinical role of adjunctive antibiotics, and expanding recognition of tocolytic complications. Laboratory investigations into the role of subclinical genital infections as causes of prematurity continue to show promise. Despite these recent scientific advances, the effective prevention and treatment of prematurity continues to elude our clinical efforts.

Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor.

A randomized prospective trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor. Forty patients with intact membranes in preterm labor at 23 to 34 weeks' gestation were randomized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent. Successful intravenous ritodrine therapy was followed by oral terbutaline therapy, and indomethacin-treated patients continued to receive oral indomethacin. Treatment failures were defined as progressive preterm labor or patient intolerance, and these patients were treated with intravenous magnesium sulfate. Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery, gestational age at delivery, delivery delayed greater than 7 days, attainment of 35 weeks of gestation, percentage of patients who required magnesium sulfate therapy, percentage of patients who were readmitted with premature rupture of membranes, absence of recurrent preterm labor, and infant birth weight. More than 80% of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects, and one patient discontinued treatment as the result of intolerance. There were minimal patient complaints with indomethacin use. No statistically significant differences were noted in neonatal outcome as defined by Apgar scores, umbilical cord pH, intensive care days, ventilator days, or neonatal deaths. However, three cases of primary pulmonary hypertension were observed in the indomethacin group. We had not previously observed this problem with short-term (24 to 48 hours) indomethacin therapy.

The safety and efficacy of tocolytic agents for the treatment of preterm labor.

Pharmacologic inhibition of uterine contractions remains the mainstay of treatment for preterm labor despite the ongoing controversy regarding its effectiveness. A diverse variety of tocolytic medications have been proposed for clinical use, with betamimetics and magnesium sulfate being the common therapeutic agents of choice in the United States today. The clinician using these agents should be aware of the significant maternal and fetal side-effects associated with these particular medications. New classes of pharmacologic agents, including prostaglandin synthetase inhibitors, calcium channel blockers and phosphodiesterase inhibitors, have been proposed as tocolytic agents and are currently undergoing critical clinical evaluation. The purpose of this review is to provide a compilation of the available clinical studies that document the safety and efficacy of these various tocolytic agents.

Doppler recording of fetal movement: clinical correlation with real-time ultrasound.

Processed Doppler signals can be used to detect fetal movements during antepartum fetal heart rate (FHR) testing. The purpose of this project was to evaluate the ability of a commercially available Doppler system, the Toitu Fetal Actocardiograph MT-320, to detect and discriminate various fetal activities during routine antepartum FHR testing. Simultaneous visualization with real-time ultrasound allowed correlation of isolated and complex fetal activities with the processed actograph signals. This apparatus was able to detect 95.9% of all major fetal movements observed, 94.3% of isolated fetal movements, 95.6% of isolated spinal flexion-extension, 97.1% of isolated rolling movements, and 100% of all multiple (P less than .001) fetal movements. Based on the amplitude (P less than .0001) and duration of the isolated actograph signals, it was possible to discriminate among fetal limb movements (mean amplitude 87.3 units, mean duration less than 2.0 seconds), spinal flexion-extension movements (66.3 units, 14.8 seconds), and rolling movements (43.8 units, 22.1 seconds). The routine detection of fetal breathing, hand movements, and rapid eye movements appears to be beyond the sensitivity of this particular apparatus. The ability to evaluate fetal activity reliably may be clinically useful during routine antepartum FHR testing.

Preterm and term fetal cardiac and movement responses to vibratory acoustic stimulation.

To assess fetal response to vibratory acoustic stimulation, 24 preterm (group A; less than 36 weeks' gestation) and 30 term (group B; greater than or equal to 36 weeks' gestation) pregnancies were studied. Study variables were perceived fetal movement, fetal heart rate, and fetal heart rate pattern. Observer- and patient-perceived fetal movement responses were noted in most cases but were slightly more common in term patients (group A: + fetal movement, patient 87.5%/observer 87.5%) group B: + fetal movement, patient 96.7%/observer 90%). Baseline changes in fetal heart rate (greater than or equal to 10 beats/min) were observed in 46% of preterm fetuses and 70% of term fetuses. Tachycardia (fetal heart rate greater than 160 beats/min) was a common finding in both groups. In group A, tachycardia after vibratory acoustic stimulation persisted more than 1 minute in 29.2% and more than 5 minutes in 12.5% of patients. In group B tachycardia beyond 1 and 5 minutes was noted in 73.3% and 50% of patients, respectively. A significant shift to "awake" fetal heart rate patterns occurred in both groups; 29% to 79% was noted in group A (p less than 0.001) and 46.7% to 90% in group B (p less than 0.001). When vibratory acoustic stimulation was used, the high occurrence of increased baseline, tachycardia, and emergence of unusual fetal heart rate patterns must be recognized to adequately interpret fetal heart rate tracings.

The effect of maternal position on uterine artery flow during antepartum fetal heart rate testing.

Uterine artery flow-velocity waveforms obtained with continuous wave Doppler techniques during nonstress testing showed no difference between the left lateral decubitus position and the supine position, suggesting no difference in uterine blood flow.

Spontaneous rupture of the renal collecting system during pregnancy: successful management with a temporary ureteral catheter.

Spontaneous rupture of the kidney or collecting system during pregnancy is an unusual condition. We report the sixteenth such case and, to our knowledge, the first case managed successfully with temporary insertion of a ureteral catheter. Based on our experience in this case, we recommend a modified approach to therapy for this condition.

The presence or absence of fetal breathing movements as a predictor of outcome in preterm labor.

The presence or absence of fetal breathing movements may be helpful in differentiating between true and false preterm labor. We attempted to demonstrate the clinical utility of this simple ultrasonic observation in predicting short-term delivery outcome during suspected preterm labor. A total of 50 pregnancies between 26 and 34 weeks' gestation with presumed preterm labor were observed in a prospective manner. During 20 minutes of observation with real-time ultrasound at the time of admission, fetal breathing movements were observed in 33 patients and considered absent in the remaining 17 patients. In those pregnancies with absent fetal breathing movements, true labor with subsequent delivery occurred in 16 patients. Of the 33 pregnancies with fetal breathing movements present, 29 continued for greater than 48 hours. It appears that the absence of fetal breathing movement is a reliable indicator of imminent preterm delivery, irrespective of fetal membrane status (p less than 0.0001). The observed mean sensitivity and specificity of this phenomenon in predicting short-term delivery outcome are 96.6% +/- 3.3% (mean +/- SD) and 80.0% +/- 8.9%, respectively. A multivariant statistical model based on the frequency of contractions, white blood cell counts, initial cervical examination results, and premature rupture of membranes could successfully predict delivery outcome in 40% to 75% of cases. The addition of fetal breathing movement analysis to the model allowed for the correct prediction of outcome in 90% of the cases.